Containers for use in an automated centrifuge

ABSTRACT

SYSTEM FOR THE SEQUENTIAL TREATMENT OF LIQUID CHEMICAL SAMPLES COMPRISING THE STEPS OF DEPOSITING THE SAMPLES IN A SERIES OF TOP-LIKE CONTAINERS HAVING A PERIPHERAL SIDE CHAMBER. THE CONTAINERS ARE PLACED ON A BELT AND MOVE PAST A CENTRIFUGAL FIELD WHEREIN THE CONTAINERS ARE ROTATED. THE CONTAINERS ARE THEN REMOVED AT A TERMINAL ZONE AND THE HEAVIER SAMPLE COMPONENT REMAINS IN THE SIDE CHAMBER AS THE LIGHTER COMPONENTS FLOW TO THE BOTTOM OF THE CONTAINER.

s. NATELsoN 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED GENTRIFUG July 30, 1974 8Sheets-Sheet 1 Filed May l5. 1972 July 30, l974 s. NATELSQN 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE Filed May 15, 1972 8Sheets-Sheet 2 FIG. 2d FllG. 2c

July 30, 1974 5, NATELSQN 3,826,622

CONTAINERS FOR USE IN AN AUI'OMATED CENTRIFUGE Filed May 15. 1972 l eSmeets-Sheet s LOADING STATION FIG. 5

MW 30, 1974 s. NATELSON $526,622

CONTAINERS FOR USE I AN AUTOMATED CENTRIFUGE 8 Sheets-Sheet 4 Filed May15. 1972 s. NATELSON 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED GENTRIFUGE July 30, 1974 8Sheets-Sheet 5 Filed May 15. 1972 s. NATELSON 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE July 30, 1974 8Sheets-Sheet 6 Filed May l5, 1972 FIG. 6

FIG. 7b

n.Fully 30, 19M s. NATELSON 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE Filed May l5, 1972 8Sheets-Sheet '7 FIG. 7e

8 Sheets-Sheet 8 5. NATELSON July 30, 1974 CONTAINERS FOR USE IN ANAUTOMATED CENTRIFUGE Filed May l5. 1972 OZ UD gUnited States .Patent 4OCONTAINERS FOR USE IN AN AUTOMATED `Samuel Natelson, Chicago, Ill.,Iassiguor to Rohe i l'Scientific'Corporation;"Sauta-Ana, Calif.

Continuation-impart of application Ser. No. 845,992, July Blk-11969, nowvPatent'No. 3,722,790. This application May 15, 1972, Ser. No. 253,1671- U.S. Cl. 23--259 This yapplication is a continuation-in-part ofpatent application ;Ser. -fNo.-845j,992, 'filed July 30, 1969, now U.S.Pat. 3,722,790.

INVENTION The present invention relates to an automated clinicallabgratoryQ-and morelpbarticularlyY toan automated clinical laboratorysystem wherein samples can be rapidly and efectively.processetknotwithstandingv the fact that the workload of samplesprocessed varies considerably over Werking pertuis-l 'if Numerousattempts have been made to design a laboratory whereblood or,` urine,,orsor ne other biological uid can be processed automatically,v Nol.complete system has been; developed: Fonfcxample, -for v`many Chemicaldeterminations. asamplepffserzum needs t to be prepared from the blood.The blood is then centrifuged and the serum sampledrfflhe'.prqcessofplacing .l a`rge numbers of tubes in a centrifuge, waiting furthevcentrifuge to accelerate, operatingfat.,highfspeedsfand then coming torest, usually takesapprpximatelyy2030minutesr To this rnust be added thetimerequiredl to load ,the` centrifuge and unload it.

`Once the serum is obtained, th automatic instrument isalaaded.Sometcommercialtinstruments do not have the capability of removingproteins. The numberA of tests that can be performed AiS'.thenflinited,ltoythose where protein does not interfere. Other instruments removeprotein by` aqdlirlig'a-Y` protein.,pgipitatingreagent and filtering.|In this case a large sample is needed and only a small portion ofthe'filtrate-is:-obtained. Others-systems remove protein by dialysis;ltlithese.c ases,=only` asmall percentage of the ingredient being testeddialyzes through, 'limiting the sensitivitytand' accuracyi'of. theprocedura so that now methodology hasgtov be Afound to; fit the`instrument. In many cases, compromise" has to' bemade with accuracyinventionf solyes K tllese4 problems, making t .automated laboratoryvusing con,- A ,A It` .permits the ,processing of the etedff,mithefpatient directly withoutfpref treatmentior 'handlmg.:Itlrreadilypermits any number Ot analysant/beneietmsdeutamatically andthe. results ha-rts vdepending upon thetogfseparate-redi-cells.fromblood automatically and remove` they serum''fro'mfsaid c'.e`lls.1 It? alsoypermits the automatic 'ice precipitationof proteins and their removal by automatic centrifugation.

Before describing the system herein contemplated, it is lirst necessaryto see what tests the system is to perform, and, since the systemcontemplated is particularly useful for processing blood samples, thetests relating to blood will be described.

It goes lwithout saying that for some tests this apparatus is notrequired. Such blood tests have been described in the Natelson, U.S.Pat. No. 3,260,413. In the tests performed by the system of the presentinvention the sample cannot be processed in the manner described in theaforesaid Natelson, U.S. Pat. No. 3,260,413 without rst separating someof the components in the sample.

The overall procedure can be. described as follows:

After separating serum or plasma from the cells, one samples theseparated serum with an autodilutor. This is an instrument which samplesthe serum and ejects it with a reagent or diluent. Autodilutors, ofvarying design, are available commercially.

After separating the serum from the cells, a series of samples can betaken from the serum and processed to (a) Glucose, by heating withalkaline determine the various components. In some cases, theautodilutor adds a protein precipitant. The mixture is then centrifuged,and an aliquot is taken from the supernatent, by an autodilutor. Variousreagents are added to produce a color so as to assay the variouscomponents.

Thus, one can see that with an automatic centrifuge the technicianplaces the blood sample, contained in a special container hereinafterdescribed, into a holder called a trunnion cup. The sample, eg., blood,is centrifuged automatically. The centrifuged blood moves down a line ona belt Where autodilutors lremove samples t0 do diierent tests. In somecases, no further reagent need be added and the diluted serum is assayeddirectly. In other cases, a sequence of sampling, centrifuging andfurther sampling is done. Examples of the various types of components ofblood which can be analyzed by a general system of the type described,are listed below.

(I) TESTS WHERE NO` PROTEIN NEEDS TO BE REMOVED FROM THE SE'RUM [n thesecases, after passing the automatic centrifuge, the separated serum issampled andprocessed as indicated.

(a) Proteinserum sampled, biuret reagent added and (e) Oxygen andnitrogen-serum sample taken and4 processed in a gas chromatograph. (f)Ca and Mg-diluted serum aspirated into an automatic absorptioninstrument.

(I'I) TESTS FOR COMPONENTS WHERE PROT-EIN 1 .IS PRECIPITATED BEFOREADDING TI-IE COLOR DEVELOPING REAGENTS f Copper, reagent. (b) Urea, bythe diacetyl reaction. (c) Creatine,.by alkaline picric acid.

(d) Uric acid, by reduction of phosphotungstic acid.

1 (III) ENZYME TESTS color or a protein precipitant is added. Thesamples are centrifuged and then reagents are added' for purposes ofidentification of the products.

The data accumulated at various stations can be accumulated on a tapeand fed into a print out device which can supply the data in the formdesired with conventional instruments. A panel, with proper keys, canguide the speciment through the system. For example, if only sugardetermination is desired on the sample, then activation of this key willmake inoperative all sampling positions except that for sugar. On theother hand, if all tests are desired, pressing the proper key willactivate all stations for the sample.

From the foregoing description, it will be noted that present technologypermits the carrying out of many of the steps described. However, onestep cannot be carried out. That step is the automatic centrifuging ofthe sample y in a continuous manner. The problem is to centrifuge thesample and have it move out of the centrifugal field. In order toperform this task one can conceive of an instrument which would performthe following steps mechanically.

(1) Place a tube in a centrifuge.

(2) Slowly accelerate the specimen to running speed (e.g.,

3000 r.p.m.).

(3) Run the rotor at top speed for ten minutes.

`(4) Decelerate the rotor.

(5) Remove the specimen from the rotor.

While there would be no diiculty in designing such an instrument withpresent technology, the problem is that such a cycle would take 30minutes and specimens would be available at two per hour. If a largenumber of specimens were available, such an instrument would load, forexample, 60 specimens, go through the cycle and at the end of say 45minutes have all 60 unloaded. Unfortunately, laboratories are faced withthe complex problem of having at some times only one specimen and atothers as much as 300. The problem is to provide an instrument whichwill process the samples sequentially. Under such a system, the sampleswould be loaded at one per 30 seconds and unloading at one every 30seconds. One would wait 20 minutes for the first specimen, butsubsequently they would be leaving at 120 per hour so that after a delayof 20 minutes the analytical results would be available at 120 bloodsamples per hour with as many as 40 results on each blood sample.

The problem is further complicated by the fact that blood is oftentalken with heparin, in which case the blood does not clot. Oncentrifuging, the packed cells are relatively loose. Further, if theserum is allowed to remain in contact with the cells for any length oftime, diusion of, for example, potassium ion from the cell(concentration 90 meq./l.) into the plasma (concentration 5 meq./l.)destroys the value of the determination. Glycolysis going on in the cellalso metabolizes the glucose in the plasma, Alowering the result. Thisrequires that the centrifuge operation -be done not once but twice. Theblood is centrifuged, the serum is poured off, recentrifuged and pouredoff again to remove all cells.

If the blood is clotted, the cells will pack more efficiently andsometimes it is possible to -pour off clear serum, if one is willing tosacrifice some serum over the clot.

From the foregoing description, it is quite apparent that the bottleneckin any completely automated system is in the centrifuging step. Thisinvention solves this problem. This invention'describes a practicalprocedure and instrumentation for continuously centrifuging samples insequence at a rapid rate.

The invention as well ,as the objects and advantages thereof will becomemore apparent from the following detailed description when takentogether with the accompanying drawings, in which:

FIG. l is a schematic and block diagram .of the system contemplatedherein;

FIG. 2a is a perspective view ofone type of sample containercontemplated herein;

FIG. 2b is a side view of the sample in FIG. 2a;

FIG. 2c shows a side view of another tainer contemplated herein; l

FIG. 2d illustrates a side view of still anothervtype ,of containercontemplated herein; v

FIG. 2e shows a perspective view of yet another typev of containercontemplated herein; l l

FIG. 2f is a side view of the container shown in FIG. 2e;

FIG. 2g is an illustration of the action that takes place containerdepicted type of conwithin the container shown in FIG. 2a while thatcon-v tainer is in operation;

FIG. 2h is an illustration of the action that takes place in thecontainer shown in FIG. 2a`after the operation illustrated in FIG. 2g; t

FIG. 2i is an illustration of-anotherY container contemplated herein;

FIG. 3 is a longitudinal perspective vievvof an appartus contemplatedherein to perform the systemv shown in FIG. l;

FIG. 3a shows an enlarged perspective view of a portion of FIG. 3; FIG.3b is a perspective view similar to FIG. 3a showing a slightly modifiedarrangement;

FIG. 3c is a cross-sectional view of a portionof the apparatus shown inFIG. 3;

FIG. 4 is a perspective explanation of a terminal station of anapparatus contemplatedl herein; Y

FIG. 5 is a schematic and block electrical circuit diagram used inconnection with the terminal station shown in FIG. 4;

FIG. 6 is a side view of another embodiment of the apparatuscontemplated herein;

FIG. 7 shows a variation of the` drive arrangement; FIG. 7a is a sideview of still another embodiment of the apparatus contemplated hereinusing the drive arrangement of FIG. 7;

FIG. 7b is a cross-sectional view of the apparatus shown in FIG. 7a;

FIG. 7c is a perspective illustration of a variation of the conceptshown in FIG. 7a;

FIG. 7d presents yet another shown in FIG. 7a; =FIG. 7e is a partlyperspective and partially sectional view of an apparatus embodying theconcepts depicted in FIGS. 7a to 7d; and l FIG. 8 is a similar view of`an actualapparatus.

variation of the conceptl for an automatic and continuous centrifugingoperation which will provide each separate samplewith the required workperiod without stopping between operations and"v furthermore provide asequential system so that one or many samples may be rapidlyandseqti'entially loaded atY one end of the apparatus and unloaded atthe'lother. A schematic and block diagram of the Vsystem is illustratedin FIG. l'which shows an apparatus 100having a revolving line 102 drivenby turning means V104 and supported by a driven element 106. Therevolving? line 102 i is designed to hold a sample container 108. Thesample"- container is rotatable and has axed thereto a rotator 110. Thissample container will be mounted on the rotating line 102 and carriedalong a path of travel having one or more work stations. One of thesework stations willbe the centrifuging -field and will have rotatorturning means 112 which lwill cause the rotator 110 to turn so as tocentrifuge any liquid in the container. After the centrifuge stationthere will be a sample container unloading station 114 where the samplecontainers are unloaded andcarried to other work stations.

The Containers FIG. 2a is the design of a collecting sample containeruseful for the purposes of the present invention. FIG. 2a shows atop-shaped round container with a central disc-shaped section 17 whichmay be called the side chamber. It will be seen that a neck 19 isprovided which can be stoppered so that the container can be evacuated.By using a double needle, one inserted in the vein of a patient and theother through a rubber stopper, blood will be aspirated into thecontainer. These containers substitute for and are used in lieu of testtubes with the ability to act as vacuum containers. As an alternative,the blood from the patient can be placed directly in the container froma syringe and the container can be stoppered. The containers 15 can bedescribed as top-shaped with a a'nged neck 19, a barrel-shaped center21, a side chamber defined by a central disc 17, a narrowing bottom 23,a cylindrical section Z5 to hold the container, with inner bottomdepressions 27 to serve as holding or spinning means.

The container shown in FIGS. 2a and 2b is designed to hold 5 ml. ofblood. These can be made in any size. They may or may not contain ananticoagulant.

l If the container shown in FIG. 2a is spun around ifs vertical axis,the blood is driven laterally by centrifugal forces taking the positionshown in lFIG. 2g. When spinning stops the serum or plasma will slidedown taking the position shown in FIG. 2h. The heavier cells, with orwithout the clot, will be driven into the side chamber, i.e., disc likesection. The disc portion has a narrow orifice of theorder of 2-3 mm. Bymeans of its design, it can be made to hold a volume somewhat largerthan the volume of the erythrocytes.

l The volume of a cylinder is given by vrrzh. If one subtracts thevolume of the inner cylindrical ring from the outer cylindrical disc,one obtains the volume held by the disc. If h is the height of the disc,R the total disc radius and r the radius of the inner ring, this volumewould be -rrR2h- 1rr2h, or vrh(R2-'r2). In FIGS. 2b and 2a, the volumeheld in the side container would be 3 ml. for a 0.3 mm. height and a 1.5cm. distance shown. This means that 3 ml. of the blood Would be in thischamber and the remainder outside. When the`rotation stops, the serum or`plasma will slide to the bottom of the container leaving the cells witha small amount of serum or plasma in the side chamber and cell freeserum or plasma at the bottom of the container. This is so because ofthe well known phenomenon that if water is placed in a tube sealed atoneY end, and with a narrow orifice, then inverting the tube will causeno liquid to ow out because it is held in by air pressure. Thisprinciple is used in perfume bottles and hairtonic bottles. One mustshake vigorously to obtain some iiow out of the bottle.

The design of the container can take the form of FIG. 2c showing acontainer 15a with the side chamber having knob-like wings 17a in whichcase a large volume can collect in the` side chamber without making thecontainer orifice unduly wide.

Other shapes are also possible and one is shown in FIG. 2d showing acontainer 15b with large wings 17b. It is also advantageous to use theconfiguration shown in FIGS. 2c and 2f with inclined wings 17o. Thecontainer with the conguration shown in FIGS. 2e and 2f have theadvantage that a narrow orifice to the side chamber is unnecessary. Whenthe container stops spinning, the erythrocytes will remain in the sidechamber held by gravity. This is particularly useful where largervolumes are used.

When spinning, the device shown in FIG. 2a will drive the cells 29 intothe outer disc (FIG. 2g). AThe cell free serum or plasma 31 will thenfall free when the spinning stops leaving the cell behind in the disc(FIG. 2h).

In subsequent operations, where a protein precipitant is added to theserum, the precipitate has strong coherence; In this case, a design suchas FIG. 2d can be used. If spun at 12,000 r.p.m. this precipitate willcollect in the corners of wings 17b and pack. On stopping the rotationthe centrifugate will drop to the bottom, the precipitate adhering tothe corners.

The type of container shown in FIGS. 2a to 2h has an additionaladvantage. If these containers are used in subsequent sampling there isno danger of picking up the cells in the pipette since they are lockedin the side chamber. This is a serious problem in sampling fromtesttubes. Further, when returning serum to the test tubes, the cells arestirred up and the tube needs to be recentrifuged. This is avoided inthe container of FIGS. 2a, 2c and 2e. The advantages of such containersmay then be summarized as follows:

(l) The tube may be spun to separate the cells from clotted or unclottedblood.

(2) The cells are separated into a separate compartment.

(3) The serum or plasma is isolated from the cells and components aretherefore more stable.

(4) Sampling from the container is done without fear of cellcontamination.

(5) Serum or plasma may be returned to the container without stirring upthe cells.

In eifect, the container becomes a serum or plasma separator. Sinceblood contains, usually from 35-47% of erythrocytes, by removing 60%,one is assured of removal of all the cells. From 5 m1., 2 ml. of clearserum or plasma is thus obtained. This is approximately what is obtainedwith conventional techniques.

The containers of FIGS. 2a-2h then permit the design of a continuouscentrifuge system. One form of this invention can Ibe seen in FIG. 3.The objective is to rotate the cups in a sequential fashion. Each cupneeds to be rotated for at least 5-10 minutes. If it is desired to havethem delivered at the rate of one every 30 seconds and spin each fortive minutes, then ten cups must be spinning at the same time.

In some cases, it is not necessary to remove the serum from the clot,after centrifugation. In this case, a simpler design can be used for thecup. This takes the form of a small Erlenmeyer flask in whichthe bottomhas been pushed up so as to create a side chamber, disposed laterally atthe bottom of the container. In this case, after centrifugation, theclot moves into the side chambers leaving the serum above it.

Thus, the containers contemplated herein for use in an automatedcentrifugal arrangement are so constructed as to be rotatable about asubstantially vertical axis and have a flanged neck, a center portion, asidechamber at least partially surrounding the center and a narrowingbottom. The ilanged neck forms a cylinder suitable for insertion of astopper with an upper wall continuous with the neck at the lower end ofthe cylinder, the upper wall making an angle greater than with the neck.`The `upper wall meets and is continuous with a lower wall so that theside chamber of the container is formed between portions of the upperand lower walls at least partially surrounding the central axis. Thecontainer will have holding means for firmly holding it in a rotatingtrunnion cup. The container may take several shapes, e.g., the sidechamber may be disc-shaped, have a pushed-up bottom,

and may also include "'a crest-like junction 4"downwards into said'si'dechamber. 1 1r 'The "cups" shown in -FIGS.' 2a-2hV show? the Aside cham'-bers-to'be"'at1diiferent angles. The rate'v of 'settling will-bcaffected by the angle the walls make with the horizontal. As 'thecups4rotate ontheir'rcentral axis the solid particles movel outward and 'ifthe vwall is vertical, 'would reach th'ei-'wall land 'stay there. Therewould be no downward component' ofthe forcef When the wall is at anangle, the reaction" of the walltonthe'particle tends to drive it backina-motion perpendicular vto the wall. This motion may be' divided-intoahorizontal or remixing component and a downward component. If the wallis at 45 to the base, then both components are equal. If the angle issubstantially greater than-.60 the downward component is small and along time will be needed for settling. In order to achieve a compromisebetween excessive width to the container and minimal mixing ondecelerating, an angle of approximately 57 is suitable for practicalpurposes.

The Processing Apparatus Friction Drive In FIG. 3 is shown an apparatus33 for rotating the containers 15. The drive apparatus 33 has a largesprocket 35, driven by a small sprocket 37, by means of a chain 39.Mounted on the chain 39 are a plurality of C-shaped brackets 41 as shownin FIG. 3a or box-like brackets as shown in FIG. 3b, having upperandlower ball bearing apertures 43, 45 holding therein a flexible rod 47disposed normal to the chain, i.e., the chain moves horizontally and therods are disposed vertically at the bottom of each rodwis an outwardlytapered rotor 49 while at the top is an open trunnion cup 51. The chain39 is engaged by the sprockets 35,l 37 and rotates slowly in thehorizontal plane driven by motor 65. At the sample loading station 53the containers e.g., those shown in FIGS. 2a-2h are loaded on thetrunnion cups.

The chain is driven by a motor 57a which rotates slowly. This turns thesprocket 37 which turns the larger sprocket 35. The large sprocket 35 ispinned on an axle 36. This motion serves to Ibring the assembly of thecontainer 15H, the trunnion cup 51, its shaft 47 and a small rotor 49around the large sprocket 35. As this assembly approaches the sprocket,the small rotor 49 engages the friction disc 61-which is moving at highspeed driven by motor 57. Since, as it approaches, it gradually makescontact 'with this disc, the rotors 49 engage slowly, and areaccelerated until they reach top speed as they move around the frictiondisc 63. This rotation will continue during the travel of the container15 around the large sprocket 35. After the cups leave the spinning area,they idle, slowing down gradually. They are then removed to a belt linefor further processing such as in a system of the type described.

Thus, the containers 15 are placed in trunnion cup 51, i.e., in holders.Each container has two little recesses 27 on the bottom (FIG. 2b) whicht into two corresponding nipples in the trunnion cup holders. The edgesof the trunnion cup are exible on the end so that when the cup isinserted, it clips over the edge serving to hold it in place. Thesetrunnion cups 51 are mounted on the chain through the bracket 41 andball bearings 43, 45. The rod 47` supporting the' cup in somewhat4ilexible so as to take advantage of the self-balancing principle wellknown to 'operators of high speed centrifuges or even laundrycentrifuges. `At the bottom of the rod is thefrotor 49 which is rubberedged. This edge is bevelled in such-a way so that lifting of t-hecentrifuge motor 57 and friction disc attached, will make contact. Thispermits adjustment so that all small rotors make contact and are stillnot too tight.

As-the friction disc 61 spins, it causes the small rotor 49 to spinunder each cup. In one model, the friction disc was seven inches acrossand t-he small rotor was one inch across, the ratio of circumferences isapproximately 21:3, o r sevenrto one. This is an advantage since 8 thecentrifugal 'motor 57 need not spin-as rapidly-.f-Tlhe higher" the speedof centrifugin'g,the faster rwill'th'e Vred cells settle. In oneapplication the friction fdisc'vwas moved atv 2000 r.p.m. causing thesmall rotor to spin at 14,000: r.p.m.'lf the' frictiondisc "i's'spunf'at'51000 r.p.m.', then the small rotor moves at 7000l r.p.m. Even at thelower speed the cells are separated inten minutes. The chain is rotatedslowly by a second motor :65.1This motor is a slow gear motor movingcounter 'to the-ro tation of the centrifugal motor. This movesthe'specimens into and out of the centrifugal eld. This gear motorsspeed is adjustable since the time required for separation of variousprecipitates is variable andin certain applications more or less time isrequired. i

The chain encompasses Vs of the large sprocket. Thus 3A; 21=approx. 15inches is available for the centrifugal operation. Since the center ofeach specimen is a 3 inch distance from its neighbor, the model couldsimultaneously spin 5 specimens. If it is desired` to have each specimento be in the centrifugal eld forten minutes, this means that the largesprocket mustmove 3/s of its circumference in ten minutes, or onerotation inV` 14 minutes. The model with this setting delivers acentrifuged specimen every two minutes.l The. rate of specimen deli-verycan be increased by increasing the size of the large rotor or decreasingthe centrifuging time. The latter is achieved by increasing the speed ofthe centrifugal motor. Rotors as large as l0 inches across havebeenfound quite practicable. Speeds up to 3600 r.p.m. of the centrifugalrotor are also practicable. The rotors are made preferably of aluminum.A silicone rubber'belt emcompasses the rotor to provide the necessaryfriction drive. If the rotors are rubber edged, the friction'disc neednot be and still maintains adequate friction for spinrnng.

After the sample has spun, the sample can be remove by hand. As a tabletop centrifuge, for a few specimens, the operator adds a few samples andsets the machine to automatic stop. When the last sample exits, theinstrument stops and the operator can pick up his specimens.

The engagement between the friction disc 61 and the small rotor used toturn the trunnion cup 51 may perhaps best be understood from FIGS. 3band 3c. In this lfigure, the motor 57 drives the friction disc 61 havinga hard silicone rubber wall 63a. Disposed for rotation above rotor drivedisc 61 is a chain 39 held by` a large sprocket 35 which engages chain39. Mounted on the outside of the chain 39 is a bearing unit 41a similarto the one shown in FIG. 3a. This bearing unit 41a holds a flexibleshaft or rod 47 having a trunnion cup 51 on top which holds thecontainer 15, and, a small rotor 49a made of metal with a rubber wall`65. The side of the rubber wall 65 is inclined and will dovetailalongside of the adjacent silicone wall 63a. .l

At the end of the run, a transfer device for removing the sample fromthe automatic centrifuge and transferring it to a belt line isnecessary. A device with some similar elements has already beendescribed in the Samuel Natelson U.S. Pat. No. 3,331,665, and the devicerequired is shown in FIG. 4.

A clamp A67 which resembles in appearance that of a spring clothes pinrotates in a circle. A cam 69 operated by a cam motor 70 rotates to liftand lower a rod 71 having a gear 72 thereon. The rod moves in a thrustbearing 72a which is fixed `in place. This gear 72 is engaged by a 1Athick driver gear 74. Gear 72 is 111/2" in thickness so that the rod canbe lifted without disengaging from gear 72. Gear 74 is operated by aturn motor 76. The clamp is 3 inches in length from jaw to axis so thatit moves in a six inch circle. When operated in conjunction with theautomatic centrifuge, motor 65 operating the sprocket of the centrifugestops when clamp is positioned over the sample container, and turn motor76 also stops. A solenoid 79 with an armature 81l is activated and theclamp 67 is lowered bythe cam over 9 thel neck 19 of the'container 15.`rThe solenoid is deactivatedandzthe conatiner is clamped. .T he cam nowraises the rod. sol thatY the container clears the trunnion cup 51.Motor. 65 andgturn motor v'76.;are reactivated and the lclamp continuesits-rotation carrying the container in 4the clamp, to a position overabelt line 83 driven by a belt-motor 85; `Whenthe. clamp. is positionedover the belt line,:;.the. belt-.line motor .85 stops as well as turnImotor 76.l The cam: lowers the container into a container holder87; Thesolenoid isreactivated releasing the containeriThe cam raises the clamp.Turn motor 76 and belt'motor :85 are reactivated and the cycle isrepeated.

The positioning of the clamp above the centrifuge holder and belt holderiscontrolled by two light and photocell assemblies-which control twotimer switches. .Theftimer `arrangement 90 is shown in FIG. 5. Referringto FIG. 5, movement of the chain of FIG. 4 between light f9.2. andphotocell 94 closes a photoswitch 96. When photoswitch` 96 is closed,relayv 98 closes. This activates timer motor 122a which moves from stopto a pin 122 whichj has a iiag.1'I'his delivers current to motor 76,which startslto` run. Whenrelay was depressed with switch closed; themotor stopped because `a rst circuit a was interruptedaThe turn lmotor76 could not run forthe time 'period that :the flag was travelling. WhentheV pin Ais finally-closed (after 8seconds) bypass is providedvthrough. a circuit b which originates behind the photo'switch'f.v Theturnmotor176.operating rotation rod 72 Ystarts andirnoves'theclamparound and out of the field .of the photoswitch. The photoswitchopens and relayV 98-isv1inactivated reactivating circuit a. Current totheftimer motorv122a isl interrupted and the tiag flips backto flagstop. The cycle is then: repeated. r@When turnmo`tor76::is `:activated asecond motor M can be attached in parallel. Thus when turn motor 76 isrunning so does motor M` `when yturn motor 76 stops so does motor M'.Thusthe automatic-centrifuge stops when the clamp is positioned overthespecimen. A third mofor can 'also be attachedto' `the 'arrangement sothat when the clamp AinterruptsV the "second photoswitch positionedabove' abeltmovingthe specimens, the movement of the belt 'stopsLThi'spermits Vthe container to be deposited in the cup. In actual .practiceit is preferable to have two independent systems. lOne stops and startsthe automatic centrifuge. The otherl starts and stops the belt. In bothcases the clamp holding the container stops at each station at the timethat station isnot moving. TheY instrument hereinbefore describedoperates in the Acircular mode. The operation can be in the linear mode.This is shown in FIG. 6 showing a belt 123 driven by gears 125 in FIG.7a showing a chain 120 driven by gears. These gears are activated bymotor and pulley attachment 12:1. This chain 120 rotates in the verticalplane, and has a series of bearings 124 holding shafts 126 therein. Theouter ends of shafts 126 have trunnion cups 128 to hold a container 15.The lower end of the shaft has a rotor member 130 similar to the smallrotor 49 of FIG. 3a. Alongside chain 120 is a plastic friction belt 132rotating in the horizontal plane driven by a motor 134. Chain 120 runsat high speeds spinning the containers 15 supported on trunnion cups.The container is first placed in the cup. It then moves across until therotor engages the plastic belt 132 which is driven by the centrifugalmotor 134. This causes the rotor to spin. As it moves falong, it movesout of the centrifugal field. The container slows down and stopsspinning. The container is then removed by the device shown in FIGS. 4and 5. The holder now moves below the belt. The gears 122 are fourinches in diameter so that as the trunnion cups move below the belt,clearance is allowed for the rotors. In the inverted position, theyclear the plastic belt so they are not spun.

In both the circular and horizontal mode contact between the rotor ofthe trunnion cup and centrifugal rotor or belt is made slowly andgradually so that the cup starts to spin at a lesser speed due toslippage. As it l0 moves on, firmer contact is made.. This has theeffect of gradually accelerating the containers and avoids splashing.

The Processing Apparatus Gas Drive The containers shown in FIG. 6 mayalso be spun by compressed air as shown in FIGS. 7a, 7b,'7c. Thearrangement shown in FIG. 7a is similar to FIG. 6 but the belt 132 andmotor 134 are removed. The belt is replaced with a source of compressedair. The rotors are replaced by turbines to spin as the air flows acrossthem. These air driven turbines consists of a housing cage 152 holding aplurality of curved radial vanes 154. The curvature of the vanes willdetermine the direction of rotation of the shaft 126. At the side ofturbine 150 is an air supply 156 consisting of a rectangular box-likeoutlet 158 fed by air, with a plurality of parallel partitions to guidethe air ow. As the turbine approaches the air supply 156 it starts torotate and continues to rotate well past the air supply 156. Thecontainer 15 is removed at the end of the run by the device of FIG. 4while the trunnion cup 128 and shaft 126 pass under the air supply. Theturbine is at the center of the belt and clears the axle connecting thegears driving the belt.

The instrument of FIG. 3 can also be modified to spin the cups bycompressed air. In this case, the friction drive 61 and motor 57 (shownin FIG.. 3c) are removed and replaced by the arrangement shown in FIG.7c. The small rotors 49 are replaced with fan blades or turbines 147. Asource of compressed air 156a blows over the turbines while they are inthe centrifugal field. In this mode, the trunnion cups are not turnedover.. The compressed air is released from radial chambers 157:1 definedin a horizontally disposed drum 157.' The centrifugal field may bedefined by blocking oif some of the chambers by a blank 15711.

As a variation of this design, the drum delivering the compressed aircan rotate. This is shown in FIG. 7d. The drum 159 delivering thecompressed air is fed by a compressed air supply 156b. The `drum 159 ismounted on a sleeve 156e which rotates while feeding air out of the drumthrough nozzles 159a. The centrifugal field is again defined this timeby a shoe 159b.

In carrying the foregoing concepts into practice, the embodimentdepicted in FIG. 7e is equite useful. The compressed air supply is fedthrough a rotating central system into passages 160 which carry thecompressed air to a position under the turbine where it is blown at theturbine byy a vertical passage 162. The travel path of the apparatus isin the horizontalplane as shown in FIG. 3. The drive is by means of achain 239a driven by a sprocket arrangement, part'of the arrangement ofsprockets 235 being shown in FIG. 7e driving the chain. Held by thechain is a bracket type bearing arrangement 241 holding a tubine 250 atthe bottom and a trunnion cup 251 over the bearing arrangement so thatthe compressed air coming out of vertical passage 162 will hit theturbine 250 and turn the trunnion cup 251. Mounted in the trunnion cup251 is a centrifugal cup lock 253. The container 15 is placed in thetrunnion cup 251 and as long as it is not spinning, the cup lock 253will not latch onto the container 15. However, the cup lock 253 isformed of an engaging portion and a heavy tail and is pivoted towardsthe engaging portion. As the trunnion cup starts to spin, the heavy tailwill tend to fly outwardly pushing the engaging portion against thecontainer 15 held in the trunnion cup. The engaging portion will engagea flange or indentation and hold the container tight. When the spinningstops, the engaging portion will release and allow the container to beremoved.

The automated centrifuge may also be used as an automated microhematocrit centrifuge. In this case, capillaries containing blood aredisposed in recesses on a plate supported on spinners. Rotation drivesthe red cells to the bottom of the capillaries and the hematocrit maythen be measured when the carriers emerge from the centri- 1 1 fuge.Another application is a micro centrifuge. In this case, a plate withholes angularly bored on the plate spins on the rotors. Small plastictest tubes are driven to the bottom as the spinners pass through theautomated centrifuge.

A variation of the instrument shown in FIG. 8 which eliminates the useof a chain uses a metal disc 802. The supports for the trunnion cup 804,806, and fan assembly 808, are mounted at the periphery of this metaldisc 802. The metal disc 802 is rotated slowly by means of a gearmotoror belt drive assembly from below or above the dise. Compressed air froman air inlet 810 and air passages 811 blows across the fans during theirtravel over a/s of the circumference of the disc. The trunnion cups 804and containers 815 contained therein rotate at high speed as they passthe compressed air area. They then slow down, their rotation beingdamped by the spinning blades in air, and come to rest when they moveout of the air jet llow area. In this mode the trunnion cup assemblymoves in a circle.

The turbine and jet assembly is also practical in this arrangement. Thejets come from a series of pipes radially disposed from the central discwhich rotates and moves along with the fans maintaining their relativeposition. When these turbine assemblies have moved through 1% of thecircle, the air jet ow in the pipe activating them is interrupted sothat the rotation ceases and the cups can be removed. The containers areheld by a centrifugal lock 817 having an inwardly biased spring 819 anda locking piece 820. The extent of the centrifugal work field may bedefined by an air cut off shoe 822.

What is claimed is:

1. A small milliliters quantity container for use in an automatedcentrifuge apparatus comprising: means for being grasped for transportcomprising a anged neck portion, a barrel-shaped center portion, a sidechamber at least partially surrounding said barrel-shaped centerportion, a narrowing bottom portion, and, means for being releasablyheld for rotation about a vertical axis through said neck portion andsaid bottom portion.

2. A container as claimed in claim 1 wherein said side chamber isdisc-shaped.

3. A container as claimed in claim 1 wherein said side chamber isknob-shaped.

4. A container as claimed in claim 1, said side chamber including acrest-like junction with said barrel-shaped center whereby uid movingout by centrifuging action from said center flows over said crest-likejunction downwards into said side chamber.

5. A small millilite'r's quantity 'container for use in an automatedcentrifuge whereby said container may berotated on its substantiallyvertical axis so as to separate materials of different density whichcomprises, means for being grasped for transport comprising a anged neckforming generally a cylinder around said vertical axis, an upper wallcontinuous with said neck at the lower end of the cylinder, said upperwall making an angle greater than degrees with said cylinder, said upperwall havinga section meeting and continuous with a lower wall so thatsaid container is formed with a side chamber between portions of saidupper and lowerwall at least partially surrounding said central axis.

6. A container as claimed in claim 5, including bottom holding means forholding firmly said container in a trunnion cup on a centrifugeapparatus during .its rotation on its axis.

7. A container as claimed in claim 5, wherein theupper and lower wallsare substantially parallel to each other in the section forming the sidechamber. t

8. A container as claimed in claim 5, wherein a depression is formed inthe center of the lower wall to forma center compartment and a crestlikejunction between said center compartment and said. side chamber, so thatiluid moving out of said center compartment, byrcentrifugal force, flowsover said crestlike junction into said side chamber so thatondeceleration, separation is maintained between the componentsseparated by the centrifugal process.

9. A container as claimed in claim 1 wherein said con` tainer comprisesa generally continuous thin wall container;

10. A container as claimed in claim 4 wherein said container comprises agenerally continuous thin wall container.

11. A container as claimed in clairn'S, wherein said container comprisesa generally continuous thin wall container.

References Cited UNITED STATES PATENTS Shapiro 23-25 3 MORRIS O. WOLK,Primary Examiner T. W. HAGAN, Assistant Examiner us. c1. xn. 23492

